Infective endocarditis in children

Author:
Sharon E O'Brien, MD
Section Editors:
David R Fulton, MD
Morven S Edwards, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Dec 2021. | This topic last updated: Dec 11, 2019.

INTRODUCTION Infective endocarditis (IE) is an infection of the

endocardium and/or heart valves that involves thrombus formation (vegetation),

which may damage the endocardial tissue and/or valves. Although uncommon in
children, it is important to identify and treat IE because of its significant morbidity
and mortality. Prompt diagnosis, rapid treatment, and recognition of complications
are imperative for optimal patient outcomes.

IE is also referred to as bacterial endocarditis because bacteria are the

predominant microbial pathogens. IE is used in this review to include both bacterial
and fungal endocarditis.

Many aspects of IE are similar in children and adults, but there are some
manifestations that are unique to children. An overview of IE in children is
presented here. A number of other topics address particular issues in detail, some
of which will be addressed here for children:
●

EPIDEMIOLOGY

Incidence — The estimated annual incidence of pediatric IE in the United States

ranges from 3.3 per 100,000 per year among infants <1 year old to 0.3 to 0.8 per
100,000 per year in older children and adolescents [1,2]. In one study, reported
rates of IE among hospitalized children ranged from 0.05 to 0.12 cases per 1000
admissions [3].
Although the rates of IE in children increased between 1960 and 2000, with
marked improvements in the survival of children with congenital heart disease
(CHD) and increased use of central venous catheters (CVC) [4-8], they appear to
have plateaued or slightly declined since 2000 [1-3]. A study evaluating pediatric
admissions data from 37 United States hospitals between 2003 and 2010 found
similar rates of hospital admissions for IE between the period before publication of
revised antibiotic prophylaxis guidelines in 2007 and the period following [3].
Risk factors — Most children with IE have an identifiable risk factor for the
disease.
Congenital heart disease — Children with CHD, especially those with cyanotic
heart disease, are at increased risk of developing IE. Underlying CHD is present in
approximately 35 to 60 percent of children with IE [2-4,9-11]. The risk of IE is
highest in patients with complex cyanotic heart disease, especially in those who
have had surgical intervention [9,12-18].
Reported incidence rates of IE in children with CHD range from 40 to 60 per
100,000 person-years, which is several orders of magnitude higher than in the
general pediatric population [14,19]. In these reports, the CHD lesions at highest
risk for IE included cyanotic lesions, endocardial cushion defect, left-sided lesions,
and ventricular septal defects (VSD). Other risk factors included cardiac surgery
within six months and age <3 years.
There appears to be an increased risk for IE in patients who undergo transcatheter
pulmonary valve replacement (eg, following repair of tetralogy of Fallot); the risk is
particularly high with bovine jugular vein prostheses [20]. This issue is discussed in
greater detail separately.
In a study of 3840 pediatric hospital admissions for IE from the Nationwide
Inpatient Sample database (2000 to 2010), 54 percent had underlying cardiac
conditions, of whom 81 percent had CHD [2]. The most common congenital heart
defect was VSD (32 percent). Cyanotic lesions accounted for 25 percent of the
CHD cases. A prosthetic valve was present in 7 percent, and other cardiac devices
were present in 4 percent.
In a similar study of 1588 pediatric hospital admissions for IE from the Kid's
Inpatient Database (2000 to 2003), the most common CHD diagnoses were
tetralogy of Fallot (20 percent), ventricular septal defect (18 percent), hypoplastic
left heart syndrome (10 percent), congenital aortic regurgitation (8 percent), D-
transposition of the great arteries (6 percent), and patent ductus arteriosus (5
percent) [9].
Central venous catheters — An indwelling CVC is another major risk factor for
pediatric IE [21]. At-risk pediatric populations for IE include critically ill and
premature infants and children with cancer or connective tissue disorders. The
increased use of CVCs in these pediatric groups appears to be a major factor for
IE [9,12,13,21,22]. The risk is similarly increased with use of other intracardiac
devices (eg, ventriculoatrial shunts, pacemakers, implantable cardioverter-
defibrillators, and prosthetic and bioprosthetic valves). In a study of 3840 pediatric
hospital admissions for IE (2000 to 2010), 7 percent of patients with underlying
cardiac conditions had a prosthetic valve and 4 percent had another cardiac device
[2]. As use of these devices becomes more common, the relative proportion of
device-related IE increases
Rheumatic heart disease — In developed countries, the incidence of rheumatic
heart disease has declined dramatically since the 1960s, and in the modern era,
rheumatic heart disease is an uncommon predisposing condition for IE in children
[4,9]. In a study of 3840 pediatric hospital admissions for IE (2000 to 2010), 15
percent of patients with underlying cardiac conditions had rheumatic heart disease
[2]. In resource-limited settings, rheumatic heart disease remains an important risk
factor.
Other risk factors — Intravenous drug abuse and degenerative heart disease,
which are important predisposing factors in the adult population, are not commonly
seen in children [4,23].

PATHOGENESIS IE is the result of a series of complex interactions

among blood-borne pathogens, damaged endothelium, fibrin, and platelets [24].

●The endocardial surface is initially injured by shear forces associated with
turbulent blood flow in children with congenital heart disease (CHD), or
indwelling central venous catheters in children without CHD.
●At the site of endothelial damage, fibrin, platelets, and occasionally red
blood cells are deposited and initially form a noninfected thrombus.
●Transient bacteremia (which occurs in normal children) or fungemia results
in adherence of microbial pathogens to the injured endocardium and
thrombus. Subsequent fibrin and platelet deposition over the infected
vegetation result in a protective sheath that isolates the organisms from host
defenses and permits rapid proliferation of the infectious agent.
Involvement of other organs is secondary to embolization or immune-mediated
processes (eg, glomerulonephritis).

MICROBIOLOGY Although a variety of microorganisms can cause IE,

staphylococci and streptococci species are the most common pathogens

associated with IE in children [2,9,25]. In the previously described Nationwide
Inpatient Sample database (2000 to 2010) study, the relative frequency of different
pathogens varied according to whether the child had underlying heart disease [2]:
●Among children with underlying heart disease:
•Staphylococcus aureus – 28 percent
•Other Staphylococcus species – 7 percent
•Viridans streptococci – 33 percent
•Other streptococci – 17 percent
•Gram-negative bacilli – 5 percent
•Polymicrobial – 11 percent
●Among children without underlying heart disease:
•S. aureus – 47 percent
•Other Staphylococcus species – 6 percent
•Viridans streptococci – 18 percent
•Other streptococci – 10 percent
•Gram-negative bacilli – 8 percent
•Polymicrobial – 12 percent
These results demonstrate the relatively high incidence of endocarditis due
to S. aureus, which is an acute fulminant process with a high mortality rate, as
compared with IE due to most other pathogens
Although patients with indwelling catheters are at risk for bacteremia with gram-
negative organisms, gram-negative bacterial endocarditis is rare. This is probably
due to the poor ability of gram-negative bacteria to adhere to the endocardium.

In neonates with IE, likely etiologic agents include S. aureus, coagulase-negative

staphylococci, Klebsiella pneumonia, and Enterobacter species, among others
[26].
Similar to adults, blood cultures remain negative in 5 to 7 percent of children with
IE [4,6,23,24,27]. Potential mechanisms include previous administration of
antimicrobial agents, inadequate microbiologic techniques, or infection with highly
fastidious bacteria or nonbacterial pathogen. Consultation with an infectious
disease expert is recommended in all cases of culture-negative endocarditis.

Fungal endocarditis is rare and is typically caused by Candida species [4].

Indwelling catheters and high glucose concentrations in parenteral nutrition have
contributed to the occurrence of fungal endocarditis, especially in premature infants
[13]. Fungal endocarditis is frequently associated with large, friable vegetations
that can embolize, producing important complications. (See 'Complications' below
and 

CLINICAL MANIFESTATIONS The clinical presentation of pediatric

IE is variable and depends upon the extent of the local cardiac disease, degree of
involvement of other organs (eg, embolization), and the causative agent.

IE is generally classified as a subacute or acute process.

●Subacute — The subacute presentation is characterized by a prolonged

course of low-grade fever and nonspecific complaints including fatigue,
arthralgias, myalgias, weight loss, exercise intolerance, and diaphoresis. The
presence of a cluster of these symptoms in a patient at risk for IE (ie, those
with preexisting heart disease or indwelling central venous catheter) should
raise the possibility of IE as a potential diagnosis. In addition, there is a risk of
immunologic sequelae, such as immune-mediated glomerulonephritis. The
less virulent pathogens, such as viridans group streptococci and coagulase-
negative staphylococci, are usually the causative agents for subacute IE.
●Acute — Acute IE is a rapidly progressive and fulminant disease. These
patients typically have high spiking fevers, and appear severely ill. An acute
presentation is commonly seen in patients with IE due to S. aureus, which
can cause rapid destruction of heart valve tissue, abscess formation, embolic
phenomena, and a rapidly progressive deterioration in hemodynamic status.
The clinical findings of IE correspond to the underlying pathologic phenomena of
bacteremia/fungemia, valvulitis, immunologic response, and embolization [24].
●Symptoms associated with bacteremia or fungemia include fever, and
vasodilation and tachycardia due to decreased systemic vascular resistance.
 ●Valvulitis may result in a new or changing murmur. In some patients,
tachypnea and hypotension are signs of heart failure, which occurs because
of perforation of a valve, chordal rupture, or poor ventricular function.
●In children with cyanotic congenital heart disease (CHD) with either a
systemic-pulmonary shunt or conduit procedure, the murmur may not
change, but a decline in systemic oxygen saturation may occur due to
obstruction of blood flow.
●Glomerulonephritis may develop in children who present with subacute IE as
a consequence of immune-mediated disease. Other immunologic sequelae
(ie, Roth's spots, Janeway lesions, and Osler nodes) are less common in
children than they are in adults. These are described in greater detail
elsewhere
●In children with IE, septic emboli are common, resulting in extracardiac
infection (eg, osteomyelitis or pneumonia) or infarction to major vessels and
organs. Emboli to the brain may result in neurologic symptoms (eg, seizures,
headache, strokes, or altered mental status). Other major organs that may be
at risk for embolic episodes include the kidney, gastrointestinal tract, limbs,
and lungs.
●In the neonate, the signs and symptoms of IE are variable and nonspecific
[28,29]. They include feeding intolerance, tachycardia, respiratory distress,
hypotension, and a new or changing murmur. Fever may not be present with
either subacute or acute IE. Those with right-sided IE in association with
central venous catheters characteristically have little clinical evidence of
disease other than persistently positive blood cultures in the setting of
appropriate antibiotic treatment [26]. Fungal IE is more common in the
newborn infant and may present as an acute fulminant disease [13]. The IE
presentation may be indistinguishable from septicemia or heart failure.

DIAGNOSIS The diagnosis of IE is based upon a careful history and

physical examination, blood culture and laboratory results, and an echocardiogram.

Diagnostic criteria — The diagnostic criteria used most commonly for the
diagnosis of pediatric IE are the modified Duke criteria, which categorize patients
as "definite IE," "possible IE," and "rejected IE" based on pathologic and clinical
criteria (table 1A-B) [24,27]:
●Pathologic criteria – One of the following two pathologic criteria are required
for the diagnosis of IE:
•Direct evidence of endocarditis based upon histologic findings
•Positive Gram stain results or cultures of specimens obtained from
surgery or autopsy
●Clinical criteria – The clinical criteria are divided into major and minor
findings (table 1B). The clinical diagnosis of definitive IE requires the
presence of either two major criteria, one major and three minor criteria, or
five minor criteria (calculator 1) [24].
The modified Duke criteria are discussed in greater detail separately.
Laboratory tests
Blood cultures — Blood cultures are performed in all patients since one of the two
major diagnostic criteria is positive blood cultures for typical organisms associated
with IE from at least two separate specimens.
A minimum of three blood cultures should be obtained over a time period of a few
hours to two days depending upon the severity of the illness. In most patients,
three blood cultures are obtained from separate venipunctures in the first 24 hours
and an additional two blood cultures in the next 24 hours if there is no growth [30].
In critically ill children, three separate venipunctures for blood cultures should be
performed as quickly as possible (with <1 hour) and empiric antibiotic therapy
started promptly. In children who are not acutely ill, antibiotic therapy can be
withheld for at least 48 hours while the blood cultures are collected [30].

Unless there has been prior antibiotic therapy, more than five blood cultures over
two days is generally not warranted. Since bacteremia is generally continuous, the
blood cultures do not have to be obtained at any particular time in the fever cycle.

It is important to obtain adequate volumes of blood for culture. However, in

children, it is often not possible to obtain the large volumes of blood (10 to 20 mL)
recommended for adults with suspected IE. In most pediatric settings, the obtained
volume of blood for culture is approximately 1 to 3 mL in infants and young children
and 5 to 7 mL in older children. If there is a limited volume of blood, preferential
culturing of the aerobic culture bottle is suggested because almost all cases of
bacterial IE are due to aerobic organisms, and culturing for anaerobes is rarely
useful.

Echocardiography — An echocardiogram should be performed on all patients in

whom there is a reasonable suspicion of IE, as it may detect the presence of a
vegetation, a major diagnostic Duke criterion (table 1B). Risk factors for IE
including preexisting heart disease, indwelling central lines, presence of prosthetic
material, persistent bacteremia, or infection with organisms most associated with
IE should prompt early evaluation. Other echocardiographic findings of IE include
intracardiac abscess, new or progressive valvular regurgitation, and, in patients
with a prosthetic valve, evidence of partial dehiscence.
In patients with IE, echocardiography can identify the size and location of a
vegetation, extent of valve damage and the degree of valvar stenosis or
regurgitation, perivalvar extension of infection, conduit or shunt obstruction,
ventricular function, and the presence of a pericardial effusion. It can be used to
serially monitor hemodynamic and valvular function, and the resolution of
vegetations in response to medical treatment. In most pediatric cases of suspected
IE, transthoracic echocardiography (TTE) is adequate to detect the presence of a
vegetation, especially in infants and younger children (<10 years and <60 kg), and
to monitor hemodynamic and valvular function. TTE is a much more sensitive
diagnostic tool in children compared with adults [24,31,32].
However, in some children, TTE provides inadequate imaging due to suboptimal
echocardiographic windows, which may be circumvented by transesophageal
echocardiography (TEE). Inadequate TTE imaging is most likely to occur in the
following patients [24]:
 ●Overweight children.
●Muscular children.
●Children with significant respiratory disease.
●Children with surgically repaired complex congenital heart disease (CHD),
as artifacts from prosthetic material (grafts and conduits) and valves may
interfere with TTE imaging [33]. Suboptimal echocardiographic windows are
frequently present in the postoperative patient.
●Children with chest wall disruption from prior surgery or trauma.
●Children with congenital anomalies involving the thoracic cage (eg, severe
pectus excavatum).
In addition, in children with aortic valve IE, TEE is superior to TTE for the detection
of aortic root abscess and therefore may be warranted if there are findings on TTE
consistent with periannular extension (eg, changing aortic root dimensions)
[30,34,35].

Both TTE and TEE may give false-negative results if the vegetations are small or if
embolization of the vegetation has occurred.

Other tests — Other nonspecific laboratory tests that are supportive of the

diagnosis of IE include:
●Low hemoglobin/hematocrit demonstrating anemia (either hemolytic or
anemia of chronic disease), which is a common feature of IE
●Elevated erythrocyte sedimentation rate and C-reactive protein indicative of
inflammation
●Urinalysis showing hematuria, proteinuria, and red cell casts is suggestive of
glomerulonephritis, a minor diagnostic criterion

Electrocardiography is generally not helpful in the diagnosis of IE with the

exception of IE with periannular extension, in which prolongation of the PR interval
or frank heart block can occur.

Chest radiography is also not useful in the diagnosis of IE. Findings that may be
seen include cardiomegaly, heart failure, and focal pulmonary infiltrates in patients
with pulmonary septic emboli.

TREATMENT In general, the principles of treatment of IE in children are

the same as in adults. In patients with acute IE, blood cultures should be obtained
as quickly as possible so appropriate antibiotic therapy can be started. Patients
with IE-associated valve dysfunction causing symptomatic heart failure and
patients with persistent fevers and bacteremia despite appropriate antibiotic
therapy may be candidates for surgical intervention.
Antibiotic regimens — Antibiotic choice, dose, and duration of treatment are
dependent upon the underlying causative microbial agent, and are discussed in
greater detail separately.
Antibiotic regimens for common bacterial pathogens in pediatric IE are summarized
in the tables:

●Viridans group streptococci and Streptococcus bovis (table 2A-D)

●Enterococci (consultation with an infectious disease specialist is
recommended (table 3))
●Staphylococci (table 4A-B)
●Gram-negative organisms
(including Haemophilus sp, Aggregatibacter sp, Cardiobacterium
hominis, Eikenella corrodens, and Kingella sp [ie, the HACEK group]) (table
5)
Culture-negative endocarditis (CNE) occurs rarely in children and may be
diagnosed when a patient has clinical or echocardiographic evidence of IE but
persistently negative blood cultures [30]. Patients with suspected CNE should be
managed in consultation with a pediatric infectious disease specialist. Important
considerations in determining the treatment regimen include prior antibiotic
exposure, route of acquisition of the infection, whether the infection is community
acquired or nosocomial, whether the valve infected is native or prosthetic, and
whether the infection is acute or subacute [30].
Surgical intervention — Determination of the need for surgical intervention
should be individualized using a multispecialty approach, including involvement of
experts in infectious disease, cardiology, and cardiothoracic surgery.
Considerations in children are generally similar to those in adults with IE. The most
common reasons for surgical intervention include congestive heart failure,
progressive valve dysfunction, and embolic phenomena [30,36,37]. Limited
pediatric data are available, and clinical practice is largely guided by adult
guidelines.
Recommendations for surgical intervention in patients with IE are reviewed in detail

elsewhere. MONITORING The following tests are helpful in monitoring

the patient's clinical course during treatment and after completion of antibiotic
therapy:
●Antimicrobial levels — Patients receiving treatment
with gentamicin or vancomycin should have blood levels for these drugs
checked at least once a week. The dose of gentamicin should be adjusted for
a target peak level of 3 to 4 mcg/mL and a trough level of <1 mcg/mL,
although higher levels may be required for some gram-negative infections
[30]. For vancomycin, the target trough level is 10 to 15 mcg/mL, though
higher levels (ie, 15 to 20 mcg/mL) may be required initially for methicillin-
resistant staphylococci. Children with renal insufficiency require dose
adjustments for these agents [30].
●Echocardiography — Repeat echocardiogram may be warranted during
treatment of IE to assess for changes in vegetations and evaluate valve and
myocardial function. This is particularly true of patients exhibiting clinical
deterioration, new murmurs, persistent fevers, or bacteremia. Once treatment
 is completed, repeat evaluation may be necessary to establish a new
baseline of valvar and myocardial function for the patient [38].
●Repeat blood cultures — Repeat blood cultures are always warranted if
there is recurrence of symptoms. Cultures performed after completion of
antibiotic therapy may be helpful to demonstrate adequacy of treatment in
certain cases (eg, in a patient with S. aureus prosthetic valve infection
associated with prolonged bacteremia); however, repeat blood cultures may
also result in isolation of a contaminant [30].

PREVENTION Strategies to prevent IE in children include oral hygiene

for prevention of oral disease and antimicrobial prophylaxis for high risk patients
when undergoing invasive procedures [30]. We provide antibiotic prophylaxis in
children who are at highest risk for IE based upon guidance from the American
Heart Association [39]. Antibiotic IE prophylactic regimens for children are
summarized in the table (table 6). Antibiotic prophylaxis for IE is discussed in detail
separately, including discussion of patient selection and relevant procedures..)

OUTCOME

Mortality — Reported mortality rates among children with IE range from 1 to 5

percent [2,3,9,11]. Mortality is highest among patients with underlying cyanotic
congenital heart disease (CHD) and with infection caused by S. aureus [2,9]. In
addition, the risk of mortality is increased in patients who develop complications
from IE, particularly heart failure, perivalvular abscess, stroke, or septic emboli with
distant abscesses.
Complications — Complications seen in children with IE are generally similar to
those seen in adults; however, as a general rule, these complications occur less
commonly in children compared with adults.
Factors that predispose to the development of complications in children with IE
include [24].
●Prosthetic cardiac valves
●Left-sided involvement
●S. aureus or fungal IE
●Previous IE
●Prolonged symptoms (≥3 months)
●Cyanotic congenital heart disease
●Systemic-to-pulmonary shunts
●Poor clinical response to antimicrobial therapy

Complications of IE include cardiac sequelae and end-organ infection or infarction

due to embolic events:

●Cardiac complications – Cardiac complications include the following:

 •Heart failure – Heart failure can be caused by perforation of the valve,
rupture of an infected chordae, or perivalvar leaks or dehiscence in
patients with prosthetic valve. Poor ventricular function often accompanies
worsening valvar regurgitation. Heart failure is the most common reason
for cardiac surgery in patients with IE. •Perivalvular abscess – Extension
of infection beyond the endothelium may result in a fistula tract or
perivalvular infection (eg, abscess), which may cause an arrhythmia or
atrioventricular heart block. Transesophageal echocardiography (TEE) is
more sensitive for detection of myocardial abscess than transthoracic
echocardiography (TTE)..)
•Extension of infection into a prosthetic shunt or conduits may occlude the
graft. These infections require surgical intervention because they rarely
respond to medical management.
●Metastatic infection – Infection at other sites can occur from septic emboli
resulting in osteomyelitis, pneumonia, or distal abscesses in the kidneys,
spleen, brain, or soft tissues.
●Stroke – Stoke occurs in 5 to 15 percent of pediatric IE cases, chiefly in the
setting of left-sided IE [2,11,40].
●Acute kidney injury (AKI) – AKI can be caused by renal infarction,
glomerulonephritis (as a result of an immune-mediated secondary process),
and drug-induced acute interstitial nephritis. AKI occurs in approximately 10
percent of pediatric patients with IE [2].
●Other embolic events, including:
•Pulmonary embolism (typically occurs in the setting of right-sided IE)
•Ischemia of the extremities
•Splenic infarction
•Visual impairment (due to embolism or due to endophthalmitis as a result
of bacteremic seeding)
•Acute myocardial infarction
The complications of IE are discussed in greater detail separately.